Obtainment and characterization of animals Pomc-/- inducible to study the role of POMC derived peptides, in differentiation and maintenance of the adrenal gland

• Grant number: 12/24129-0
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2013 - October 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Claudimara Ferini Pacicco Lotfi
• Grantee: Claudimara Ferini Pacicco Lotfi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Jose Donato Junior ; Maria Teresa Machini ; Pedro Omori Ribeiro de Mendonça

Abstract

Studies in knockout animals for the pro-opiomelanocortin gene (POMC-/-) have been demonstrated that animals, which survive to adulthood, presented obesity, defects in pigmentation and severe adrenal insufficiency. At newborn age, adrenal gland was macroscopically present, however, five weeks after birth the gland showed a severe atrophy of the entire organ, reflecting the dependency of POMC derived peptides for the differentiation, maturation and maintenance of the adrenal gland. The adrenocorticotropic hormone (ACTH) is considered the main peptide derived from POMC that acts in the development, maintenance or steroidogenesis on the adrenal gland. Although there are some evidences, including from our group, that peptides derived from the N-terminal potion of POMC (N-POMC) may act to maintain the adrenal gland, through the induction of adrenal cortex proliferation, it remains unknown the role and importance of these peptides in the differentiation, maturation, and function of the adrenal cortex. This project aims to obtain conditionally knock-out animals, using Cre-Lox system associated with tamoxifen induction, in order to silence the POMC gene at different ages/times of adrenal differentiation. Also it will evaluate the role of different types and sizes of N-terminal POMC peptides, including synthetic or derived from pituitary extracts, in the architecture of the adrenal cortex, gland function, food intake and body weight alteration during the adrenal gland differentiation that occurs after birth. The architecture of the gland will be analyzed by immunofluorescence using antibodies to detect proliferating cells, apoptotic cells, steroidogenic enzymes, marker for fetal zone (zone X), besides the detection of extracellular matrix proteins and vessels. The functional capacity of the adrenal gland will be analyzed by quantification of corticosterone and aldosterone concentration in blood plasma. The results obtained will contribute to elucidate the role of N-terminal peptides of POMC in the differentiation and function of the adrenal gland. (AU)